Abstract
Dementia is an ominous neurological disease. Scientists proposed a link between its occurrence and the presence of Toxoplasma gondii (T. gondii). The long-term sequels of anti-Toxoplasma premunition, chiefly dominated by TNF-α, on the neurons and their receptors as the insulin-like growth factor-1 receptor (IGF-1R), which is tangled in cognition and synaptic plasticity, are still not clear. IGF-1R mediates its action via IGF-1, and its depletion is incorporated in the pathogenesis of dementia. The activated TNF-α signaling pathway induces NF-κβ that may induce or inhibit neurogenesis. This study speculates the potential impact of anti-Toxoplasma immune response on the expression of IGF-1R in chronic cerebral toxoplasmosis. The distributive pattern of T. gondii cysts was studied in association with TNF-α serum levels, the in situ expression of NF-κβ, and IGF-1R in mice using the low virulent ME-49 T. gondii strain. There was an elevation of the TNF-α serum level (p value ≤ 0.004) and significant upsurge in NF-κβ whereas IGF-1R was of low abundance (p value < 0.05) compared to the controls. TNF-α had a strong positive correlation with the intracerebral expression of NF-κβ (r value ≈ 0.943, p value ≈ 0.005) and a strong negative correlation to IGF-1R (r value -0.584 and -0.725 for area% and O.D., respectively). This activated TNF-α/NF-κβ keeps T. gondii under control at the expense of IGF-1R expression, depriving neurons of the effect of IGF-1, the receptor's ligand. We therefore deduce that T. gondii immunopathological reaction may be a road paver for developing dementia.
Highlights
Dementia is a progressive neurodegenerative disease that is characterized by irreversible neuronal losses [1]
T. gondii was capable of being incorporated into the cerebral tissues in the form of a cystic stage as shown in Figure 1, which is remarkable for the chronicity of the parasite
In chronic toxoplasmosis infection (ME-49 strain), (1) the cyst stage showed higher prevalence in the hippocampus and the amygdala when compared with other brain areas, (2) establishment of chronic toxoplasmosis occurs under the umbrella of TNF-α/NF-κβ, (3) TNF-α and NF-κβ are positively correlated, and (4) cerebral cells were deprived of insulin-like growth factor-1 receptor (IGF-1R) expression along with this parasitic infection
Summary
Dementia is a progressive neurodegenerative disease that is characterized by irreversible neuronal losses [1]. During the recent decades, interventional epidemiology in neuroscience has been introduced where the possible interaction between the pathogenesis of dementia and various individual/environmental factors is studied, and different therapeutic protocols will be determined for various patients’ subgroups [4]. In this context, identifying new targets for this disease is a matter of urgency [5]. Pathogenic agents, including Toxoplasma gondii (T. gondii) [6], Herpes simplex virus-1 [7], and Chlamydia pneumoniae [8], were thought to be implicated in the pathogenesis of some neurodegenerative diseases
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